Heat shock protein 70 as an indicator of early lung injury caused by exposure to arsenic.
Han-S; Nath-J; Vallyathan-V
Toxicologist 2004 Mar; 78(S-1):236
Heat shock proteins (HSPs) are a family of highly conserved proteins that are induced by stress, temperature, redox status, heavy metals, and inflammation. HSPs play a major role within a cell from folding of synthesized proteins or its degradation by proteosome. Intracellular transport and defects in folding can cause accumulation of these proteins resulting in several disease processes. HSP expression can be interpreted as an early and sensitive biomarker of cells in stress. Arsenic (As) is a naturally occurring metal that is distributed widely in the environment and is used in several industries. Exposure to As is associated with the development of pulmonary and skin cancers. The present study was undertaken to evaluate the expression levels of Hsp70 protein and mRNA induced by exposure to As which could be a sensitive and early biomarker. In addition, the cellular and molecular mechanisms of Hsp70 expression by As were investigated in the human bronchial cell line BEAS-2B. Cytotoxicity, lipid peroxidation and hydrogen peroxide generation were measured as indicators of cell injury and perturbed oxidative metabolism by As. Exposure of BEAS-2B cells to As(III) was associated with increased expression of Hsp70 protein and mRNA in a time and dose dependent manner. Hsp70 protein expression showed a significant five-fold increase by Western blot analysis and was increased 20-fold using an ELISA assay at a 50 uM As(III) concentration with a 6 hr exposure and an 8 hr recovery time. Hsp70 mRNA expression showed a 28% increase compared to controls. Cytotoxicity resulting from As(III) increased with a longer exposure time (48 hr). Lipid peroxidation increased six-fold at a concentration of 20 uM As(III) for 24 hr exposure, while H2O2 generation showed a two-fold increase. These results suggest that the induction of Hsp70 was the most sensitive indicator of cell injury by As(III), and Hsp70 may be a valuable indicator of oxygen free radical-induced lung cell injury.
Lung-disorders; Arsenic-compounds; Exposure-levels; Biomarkers; Proteins; Metals; Cancer; Pulmonary-system-disorders; Respiratory-system-disorders; Stress; Skin-disorders; Cell-damage; Cytotoxicity
Research Tools and Approaches: Cancer Research Methods
The Toxicologist. Society of Toxicology 43nd Annual Meeting and ToxExpo, March 21-25, 2004, Baltimore, Maryland